Using Genetic Tools to Dissect Neural Circuits for Social Communication

使用遗传工具剖析社交沟通的神经回路

基本信息

批准号：
10152701
负责人：
Richard D Mooney
金额：
$ 51.39万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-11 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10152701
关键词：
Acoustics Adult Affect Brain Calcium Chemicals Communication Data Disease Electrophysiology (science)Female Foundations Future Genetic Human Image Impairment Individual Influentials Link Mammals Maps Measures Medial Mediating Mental disorders Methods Midbrain structure Monitor Mus Neurodevelopmental Disorder Neurons Pattern Perception Play Prefrontal Cortex Production Research Role Schizophrenia Signal Transduction Social Environment Social Functioning Social Interaction Social Work Testing Ultrasonics autism spectrum disorder behavior measurement cortex mapping genetic approach imaging modality in vivo calcium imaging in vivo imaging innovation insight male midbrain central gray substance mind control mouse model neural circuit neuropsychiatric disorder novel optogenetics relating to nervous system response skills social social attachment social communication social deficits sound stem tool virus genetics vocalization

项目摘要

Project Summary An inability to form and maintain social bonds typifies a wide range of neuropsychiatric and neurodevelopmental disorders. These social deficits stem in large part from impaired expressive and receptive vocal communication skills. Surprisingly, exactly how vocal communication promotes social affiliation is not well understood, in part because the underlying neural circuits remain poorly described. Here we propose the use of a novel genetic approach to selectively tag neurons that are active during social encounters that elicit vocalizations. We will combine this innovative method with in vivo imaging, electrophysiology, chemical and optogenetic perturbations of neural activity, and behavioral measurements to identify neural circuits that facilitate expressive and receptive aspects of vocal communication in the service of social affiliation. In Aim 1, we will test the idea that a specific subpopulation of neurons in the midbrain periaqueductal gray (PAG) is required for male and female mice to produce vocalizations used during their social interactions. In Aim 2, we will manipulate the activity of these PAG neurons to suppress or augment vocalization, allowing us to test the idea that these vocalizations promote social affiliation. In Aim 3, we will test the idea that prefrontal cortical (PFC) neurons that provide input to PAG vocalization neurons are important in regulating vocalization as a function of social context. In Aim 4, we will either reversibly silence or image PFC neurons that provide input to the PAG to test the idea that they play a role in generating affiliative social responses in males and females listening to a vocalizing individual. These studies will identify the neurons and circuits that gate vocalization during social encounters and promote social affiliation in response to these acoustic signals. This research will also build the foundation for future studies that explore how these circuits are affected in mouse models of neuropsychiatric disorders characterized by social communication and affiliation deficits, such as autism spectrum disorder and schizophrenia.

项目摘要无法形成和维持社会纽带代表着广泛的神经精神病学和神经发育障碍。这些社会缺陷在很大程度上源于表现力和容忍性的受损人声沟通技巧。令人惊讶的是，确切的声音交流如何促进社会隶属关系不是良好的理解，部分是因为潜在的神经回路的描述仍然很差。在这里我们提出使用一种新型的遗传方法来有选择地标记在激发社会相遇中活跃的神经元发声。我们将将这种创新方法与体内成像，电生理学，化学和神经活动的光遗传学扰动和行为测量，以识别神经回路在社会隶属关系中促进声音交流的表达和接受方面。在AIM 1中，我们将测试以下观点，即中脑周长灰色（PAG）中神经元的特定亚群为雄性和雌性小鼠在社交互动期间使用发声所必需。在AIM 2中，我们将操纵这些PAG神经元的活动以抑制或增强发声，从而使我们能够测试这些发声促进社会隶属关系的想法。在AIM 3中，我们将测试前额叶皮质的想法（PFC）为PAG发声神经元提供输入的神经元在调节发声作为一种社会环境的功能。在AIM 4中，我们要么可逆地沉默或图像PFC神经元，该神经元可提供输入测试他们在产生男性和女性的隶属性社会反应中发挥作用的想法的PAG 听一个发声的人。这些研究将识别出发声的神经元和电路在社交相遇期间，并促进了对这些声学信号的响应。这项研究会还为将来的研究奠定了基础，该研究探讨了这些电路在鼠标模型中如何影响具有社会交流和隶属缺陷的特征的神经精神疾病，例如自闭症谱系障碍和精神分裂症。